Cis-Platinum(II) amine ascorbate complexes

Abstract

There are described ascorbate complexes of platinum(II) coordinated to ammonia, a monodentate amine ligand or a bidentate amine ligand as, for example, an alkylamine, an alkylenediamine or a cycloalkylamine. Said complexes are useful in the treatment of malignant tumors in animals and they are characterized by high solubility in water and low toxicity.

What is claimed is: 
     
       1. A cis-diamineplatinum(II) ascorbate compound of the formula:   cis-[Pt(II)A.sub.2 (X).sub.m (OH).sub.n ]     wherein Pt is in valence state II and is coordinated to A in a cis configuration; A is ammonia or a monodentate alkylamine ligand; A 2  is a bidentate diamine ligand; X is the ascorbate moiety; m is a number having a value of from 1 to 2; n is a number having a value of from 0 to 1, and the sum of m+n is not greater than 2.   
     
     
       2. A compound according to claim 1 wherein A has the formula RNH 2  and R is selected from the group consisting of hydrogen or lower alkyl. 
     
     
       3. A compound according to claim 2 wherein R is hydrogen. 
     
     
       4. A compound according to claim 2 wherein R is lower alkyl. 
     
     
       5. A compound according to claim 4 wherein R is methyl. 
     
     
       6. A compound according to claim 1 wherein A 2  is represented by the formula: ##STR3## wherein each of R 1  and R 2 , taken separately, is selected from the group consisting of hydrogen and lower alkyl, or R 1  and R 2 , taken together, afford a 1,2-diaminocycloalkane ligand containing from about 4-8 nuclear carbon atoms which may be optionally substituted by one or more linear or branched chain lower alkyl groups. 
     
     
       7. A compound according to claim 6 wherein each of R 1  and R 2  is hydrogen. 
     
     
       8. A compound according to claim 6 wherein A 2  is 1,2-diaminocyclohexane. 
     
     
       9. A pharmaceutical composition effective for treating animal malignant tumor cells sensitive to a platinum compound of claim 1 comprising an effective amounts of a compound of claim 1 in combination with a non-toxic pharmacologically acceptable inert carrier or diluent. 
     
     
       10. The composition of claim 9 wherein the active ingredient is selected from the group consisting of cis-diamineplatinum(II) ascorbate and cis-bis(lower alkylamine)platinum(II) ascorbate. 
     
     
       11. The composition of claim 10 wherein the active ingredient is cis-diamineplatinum(II) ascorbate. 
     
     
       12. The composition of claim 10 wherein the active ingredient is cis-bis(lower alkylamine)platinum(II) ascorbate. 
     
     
       13. The composition of claim 12 wherein the active ingredient is cis-bis(methylamine)platinum(II) ascorbate. 
     
     
       14. The composition of claim 9 wherein A 2  in the complex: cis-[Pt(II)A 2  (X) m  (OH) n  ] represents a bidentate amine ligand of the formula: ##STR4## wherein each of R 1  and R 2 , taken separately, is selected from the group consisting of hydrogen and lower alkyl, or R 1  and R 2 , taken together, afford a 1,2-diaminocycloalkane ligand containing from about 4-8 nuclear carbon atoms which may be optionally substituted by one or more linear or branched chain lower alkyl groups. 
     
     
       15. The composition of claim 14 wherein the active ingredient is ethylenediamineplatinum(II) ascorbate. 
     
     
       16. The composition of claim 14 wherein the active ingredient is 1,2-diaminocyclohexaneplatinum(II) ascorbate. 
     
     
       17. The composition of claim 9 wherein the complex: cis-[Pt(II)A 2  (X) m  (OH) n  ] represents a mixture of cis-diamine-platinum(II) ascorbate compounds. 
     
     
       18. The composition of claim 9 in a form suitable for parenteral administration. 
     
     
       19. The composition of claim 9 in a form suitable for oral administration. 
     
     
       20. The composition of claim 19 in the form of a tablet. 
     
     
       21. The composition of claim 19 in capsule form. 
     
     
       22. The composition of claim 9 wherein the active ingredient is present in an amount of from about 10-450 mg/kg.